Chronic stress exacerbates impairment of spatial long-term memory in LPA1-null mice
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1
University of Malaga, Facultad de Psicología, Spain
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2
The Scripps Research Institute , Department of Molecular Biology, United States
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3
Fundacion IMABIS, Hospital Carlos de Haya, Laboratorio de Investigacion, Spain
Lysophosphatidic acid (LPA) has emerged as a new regulatory molecule in the brain. Recently, some studies have demonstrated a role for this molecule and its LPA1 receptor in the regulation of plasticity and neurogenesis in the adult brain. However, no systematic studies have been conducted to investigate whether the LPA1 receptor is involved in behavior. We studied the effects of the absence of lysophosphatidic acid receptor LPA1, alone or in combination with chronic stress (immobilization in plexiglass tubes for 21 days (3 h/day)) using male LPA1 receptor knockout (KO) and wild type (WT) mice. We hypothesized that chronic stress affects diferently the hippocampal function in both genotypes. In order to study this hypothesis the mice were trained in a hole board test to assess both spatial long-term (LTM) and working memory (WM). Our data indicate that the absence of LPA1 receptor impairs spatial LTM. In addition, KO mice showed an impairment in the WM task only during the first and second training days, likely associated with the acquisition of the WM rule. Hippocampal BDNF mRNA levels were increased in both WT and KO mice, but WT mice showed greater enhancement than KO mice. After immobilization WT mice showed an impairment mainly in the LTM task. Interestingly, the strongest spatial LTM impairment was observed when KO mice were training in the hole board after immobilization. In addition, immobilization did not potentiate the spatial WM deficits previously observed in KO mice. Our results suggest that LPA1 receptors play an important role in the formation of spatial LTM. In addition, the interaction between the absence of LPA1 receptor and chronic stress impairs the hippocampal-dependent memory.
This work was supported by SEJ2007-61187, FIS exp.07/0629, CTS433, CTS065 and AP-2006-02582).
Conference:
41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009.
Presentation Type:
Poster Presentation
Topic:
Poster presentations
Citation:
Javier-Santin
L,
Castilla-Ortega
E,
Hoyos
C,
Sanchez-Lopez
J,
Pedraza
C,
Inmaculada-Garcia
M,
Chun
J,
Rodriguez-de-Fonseca
F and
Estivill
G
(2009). Chronic stress exacerbates impairment of spatial long-term memory in LPA1-null mice.
Conference Abstract:
41st European Brain and Behaviour Society Meeting.
doi: 10.3389/conf.neuro.08.2009.09.290
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Received:
15 Jun 2009;
Published Online:
15 Jun 2009.
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Correspondence:
Luis Javier-Santin, University of Malaga, Facultad de Psicología, Málaga, Spain, luis@uma.es